The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to estrogen.
The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to estrogen.
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DOI：
10.1210/endo.136.3.7867585
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发表时间：
1995-03
期刊：
影响因子：
4.8
通讯作者：
G. Prins;L. Birch
中科院分区：
文献类型：
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作者：
G. Prins;L. Birch
对新生大鼠短暂给予雌激素可永久性地标记成年前列腺雄激素受体（AR）以叶特异性方式表达。为了描述这种影响，我们研究了早期雌激素暴露对发育中的腹侧、背侧和侧前列腺叶中AR模式变化的直接影响。抗大鼠AR（PG-21）抗体与几种细胞特异性抗原抗体联合使用，通过免疫细胞化学进行阳性细胞鉴定。出生时，腹侧前列腺的间充质细胞呈强AR阳性（AR+）。上皮细胞只对基底细胞角蛋白染色，与早期报道相反，许多在第1天为AR+。在第3-5天之间，导管周间充质细胞分化成平滑肌细胞，其保留强AR+染色，而导管间成纤维细胞显示AR+细胞的发生率降低。在第5-10天之间，腔上皮细胞首先出现，并且相对于基底细胞中的AR染色强度显著增加。在青春期，基底细胞失去了AR免疫反应性。在背叶和侧叶中观察到类似的变化。新生大鼠在第1、3和5天给予25微克苯甲酸雌二醇，然后处死。到第6天，AR染色显着降低到弱到中等强度的所有细胞类型，到第10天，AR几乎是不存在的单独的叶。生长和上皮细胞分化显着延迟。在第15-30天之间，观察到管腔细胞分化的证据;然而，这通常与AR染色增加无关。在腹侧和背侧叶，连续的外周层AR阴性基底细胞包围在中央和近端区域的导管，这与腔上皮细胞表达AR的永久性无能有关。仅在远端头端观察到上皮和平滑肌AR表达。相反，AR表达迅速返回的所有区域的侧叶，除了近端导管。我们的结论是：1）基底上皮细胞早在出生后第1天就表达AR，应该被认为是前列腺形态发生过程中雄激素作用的可能直接靶点; 2）分化为管腔细胞与AR表达的增加有关，而不是诱导;和3）导管周围平滑肌细胞在整个发育过程中保持强AR表达，并且应该被认为是雄激素介导的形态发生的主要靶。新生儿雌激素最初下调三个叶的所有细胞中的AR表达，这可以解释总体生长迟缓。（400字处截断摘要）
Brief administration of estrogen to newborn rats permanently imprints adult prostatic androgen receptor (AR) expression in a lobe-specific manner. To delineate this effect, we examined the immediate effects of early estrogen exposure on the changing AR pattern in the developing ventral, dorsal, and lateral prostate lobes. Antibodies against rat AR (PG-21) were used in combination with several antibodies to cell-specific antigens for positive cellular identification by immunocytochemistry. At birth, mesenchymal cells of the ventral prostate were strongly AR positive (AR+). Epithelial cells stained only for basal cell cytokeratins and, in contrast to earlier reports, many were AR+ on day 1. Between days 3-5, periductal mesenchymal cells differentiated into smooth muscle cells which retained strong AR+ staining, whereas interductal fibroblasts exhibited a decreased incidence of AR+ cells. Between days 5-10, luminal epithelial cells first appeared, and a striking increase in AR staining intensity was noted relative to that in the basal cells. During puberty, basal cells lost their AR immunoreactivity. Similar changes were observed in the dorsal and lateral lobes. Newborn rats were given 25 micrograms estradiol benzoate on days 1, 3, and 5 and were killed thereafter. By day 6, AR staining was markedly decreased to a weak to moderate intensity in all cell types, and by day 10, AR was virtually absent in the separate lobes. Growth and epithelial cytodifferentiation were significantly retarded. Between days 15-30, evidence of luminal cell cytodifferentiation was noted; however, this was frequently not associated with an increase in AR staining. In the ventral and dorsal lobes, a continuous peripheral layer of AR-negative basal cells surrounded the ducts in the central and proximal regions, and this was associated with a permanent inability of luminal epithelial cells to express AR. Epithelial and smooth muscle AR expression was observed only in the distal tips. In contrast, AR expression rapidly returned in all regions of the lateral lobes, except the proximal ducts. We conclude that 1) basal epithelial cells express AR as early as day 1 of life and should be considered as possible direct targets of androgen action during prostate morphogenesis; 2) differentiation into luminal cells is associated with an increase, rather than an induction, of AR expression; and 3) periductal smooth muscle cells retain strong AR expression throughout development and should be considered primary targets for androgen-mediated morphogenesis. Neonatal estrogen initially down-regulates AR expression in all cells of three lobes, which may explain the overall growth retardation.(ABSTRACT TRUNCATED AT 400 WORDS)